• Biomarker detection
• Computational genomics
• Evolutionary algorithms
• Gene selection
• Simulated annealing

• Gene expression
• Metabolic syndrome
• Nile rats
• Oil palm phenolics
• Water-Soluble Palm Fruit Extract

• Animals
• Plant Extracts/pharmacology
• Plant Extracts/chemistry
• Liver/drug effects
• Liver/metabolism
• Arecaceae/chemistry
• Fruit/chemistry
• Hypoglycemic Agents/pharmacology
• RNA-Seq
• Gene Expression Profiling
• Transcriptome/drug effects
• Blood Glucose
• Rats
• Male
• Insulin Resistance/genetics

• PROFENOLIS (2011101805) Eleventh Malaysia Plan (RMK11)
• Foster Biomedical Research Laboratory funds for research Brandeis University
• teaching Brandeis University

This study aims to obtain the transcriptomes profile associated with avoiding immune destruction from nasopharyngeal cancer patients in Indonesia using next-generation sequencing.

The samples are divided into two types of samples; 1) biopsy of nasopharyngeal cancer tissue samples, 2) brushing tissue of people without nasopharyngeal cancer as control samples. The sequencing results were mapped (HISAT2) and quantified (HTSeq) for differential expression analysis using edgeR software. Transcripts data analyzed with Pantherdb and DAVID software to find genes related to the immune system and pathways related to immune destruction by cancer.

The differential expression results show that 2,046 genes that have a significant differential expression. The 90 genes expression has down-regulated and 1,956 genes expression up-regulated, there are 20 genes related to the immune system. The 20 genes related to the immune system by analyzing lionproject.net that directly related to hallmark avoiding immune destruction that genes are CXCL9/10/11. The gene expression of CXCL9/10/11 regulates PD-L1 expressions via the Jak/STAT signaling pathway. The interaction between the extracellular domain PD-1 and PD-L1 in cancer cells have avoiding immune destruction.

The results of this study suggest that the gene expression of CXCL9/10/11 have up-regulated is related to avoiding immune destruction that can use as an early detection biomarker of nasopharyngeal cancer in Indonesian patients.

• Keywords: nasopharyngeal cancer
• avoiding immune destruction
• next-generation sequencing
• transcriptomic

FAM46B is a member of the family with sequence similarity 46. Little is known about the expression and functional role(s) of FAM46B in prostate cancer (PC). In this study, the expression of FAM46B expression in The Cancer Genome Atlas, GSE55945, and an independent hospital database was measured by bioinformatics and real-time PCR analysis. After PC cells were transfected with siRNA or a recombinant vector in the absence or presence of a β-catenin signaling inhibitor (XAV-939), the expression levels of FAM46B, C-myc, Cyclin D1, and β-catenin were measured by western blot and real-time PCR. Cell cycle progression and cell proliferation were measured by flow cytometry and the CCK-8 assay. The effects of FAM46B on tumor growth and protein expression in nude mice with PC tumor xenografts were also measured. Our results showed that FAM46B was downregulated but that β-catenin was upregulated in patients with PC. FAM46B silencing promoted cell proliferation and cell cycle progression in PC, which were abrogated by XAV-939. Moreover, FAM46B overexpression inhibited PC cell cycle progression and cell proliferation in vitro and tumor growth in vivo. FAM46B silencing promoted β-catenin protein expression through the inhibition of β-catenin ubiquitination. Our data clearly show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of β-catenin.

A little-studied protein may help in early diagnosis and treatment of prostate cancer (PC), one of the most common cancers in men. Because early-stage PC causes few symptoms, many patients are not diagnosed until later stages, when treatment options are limited. New methods for early diagnosis and treatment are actively sought. Proteins in the FAM46 family are known to be involved in many types of cancer. Dongliang Yan at Shanghai Sixth People’s Hospital East and co-workers investigated what role one protein in this family, FAM46B, might play in PC. Analysis of tumor samples showed that FAM46B levels were much lower in PC than in healthy tissues. These changes were linked to another tumor-associated protein, β-catenin. In further tests in mice, artificially increasing FAM46B levels decreased tumor size. These results could improve treatments for PC.

FAM13C, a gene with unknown function is included in several mRNA signatures for prostate cancer aggressiveness. To understand the impact of FAM13C on prognosis and its relationship to molecularly defined subsets, we analyzed FAM13C expression by immunohistochemistry on a tissue microarray containing 12,400 prostate cancer specimens. Results were compared to phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. FAM13C was detectable in cell nuclei of cancerous and non-neoplastic prostate cells. 67.5% of 9,633 interpretable cancers showed FAM13C expression: strong in 28.3%, moderate in 24.6% and weak in 14.6%. Strong FAM13C expression was linked to advanced pT stage, high Gleason grade, positive lymph node status, and early biochemical recurrence (p < 0.0001 each). FAM13C expression was associated with TMPRSS2:ERG fusions. It was present in 85% of ERG positive but in only 54% of ERG negative cancers (p < 0.0001), and in 91.1% of PTEN deleted but in only 69.2% of PTEN non-deleted cancers (p < 0.0001). The prognostic role of FAM13C expression was independent of classical and quantitative Gleason grade, pT stage, pN stage, surgical margin status and preoperative PSA. In conclusion, the results of our study demonstrate that expression of FAM13C is an independent prognostic marker in prostate cancer. Finding FAM13C also in non-neoplastic prostate tissues highlights the importance of properly selecting cancer-rich areas for RNA-based FAM13C expression analysis.

• FAM13C
• immunohistochemistry
• prognosis
• prostate cancer

• DNA methylation
• hepatocellular carcinoma
• review
• tumor suppression

Epigenetic alterations have been identified as a major characteristic in human cancers. Advances in the field of epigenetics have contributed significantly in refining our knowledge of molecular mechanisms underlying malignant transformation. DNA methylation and microRNA expression are epigenetic mechanisms that are widely altered in human cancers including hepatocellular carcinoma (HCC), the third leading cause of cancer related mortality worldwide. Both DNA methylation and microRNA expression patterns are regulated in developmental stage specific-, cell type specific- and tissue-specific manner. The aberrations are inferred in the maintenance of cancer stem cells and in clonal cell evolution during carcinogenesis. The availability of genome-wide technologies for DNA methylation and microRNA profiling has revolutionized the field of epigenetics and led to the discovery of a number of epigenetically silenced microRNAs in cancerous cells and primary tissues. Dysregulation of these microRNAs affects several key signalling pathways in hepatocarcinogenesis suggesting that modulation of DNA methylation and/or microRNA expression can serve as new therapeutic targets for HCC. Accumulative evidence shows that aberrant DNA methylation of certain microRNA genes is an event specifically found in HCC which correlates with unfavorable outcomes. Therefore, it can potentially serve as a biomarker for detection as well as for prognosis, monitoring and predicting therapeutic responses in HCC.

• DNA methylation
• MicroRNA
• Epigenetics
• Hepatocellular carcinoma
• Biomarker

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/metabolism
• Cell Transformation, Neoplastic/pathology
• DNA Methylation
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Genetic Predisposition to Disease
• Genomics/methods
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Phenotype
• Signal Transduction

• Aristaless-like homeobox-4
• DNA methylation
• lung cancer
• tumor suppressor

LIM homeobox domain 6 (LHX6) is a putative transcriptional regulator that controls the differentiation and development of neural and lymphoid cells. However, the function of LHX6 in cancer development remains largely unclear. Recently, we found that LHX6 is hypermethylated in lung cancer. In this study, we analysed its epigenetic regulation, biological functions, and related molecular mechanisms in lung cancer. Methylation status was evaluated by methylation-specific PCR and bisulfite genomic sequencing. LHX6 mRNA levels were measured in relation to the methylation status. The effects of LHX6 expression on tumourigenesis were studied in vitro and in vivo. LHX6 was readily expressed in normal lung tissues without methylation, but was downregulated or silenced in lung cancer cell lines and tissues with hypermethylation status. Treatment of lung cancer cells with the demethylating agent 5-aza-2′-deoxycytidine restored LHX6 expression. Moreover, LHX6 hypermethylation was detected in 56% (52/93) of primary lung cancers compared with none (0/20) of the tested normal lung tissues. In lung cancer cell lines 95D and H358, forced expression of LHX6 suppressed cell viability, colony formation, and migration, induced apoptosis and G1/S arrest, and inhibited their tumorigenicity in nude mice. On the other hand, knockdown of LHX6 expression by RNA interference increased cell proliferation and inhibited apoptosis and cell cycle arrest. These effects were associated with upregulation of p21 and p53, and downregulation of Bcl-2, cyclinD1, c-myc, CD44, and MMP7. In conclusion, our results suggest that LHX6 is a putative tumour suppressor gene with epigenetic silencing in lung cancer.